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Abstract Background Prader-Willi syndrome (PWS) is a rare genetic neurodevelopmental disorder. Individuals with PWS face a range of cognitive, behavioral, and emotional challenges that require comprehensive and lifelong care, posing significant demands on their caregivers. The study is not only aimed to assess the psychological conditions of caregivers of adult subjects with PWS focusing on psychological distress and coping, but also to shed light on a crucial yet often overlooked aspect of healthcare. This study aims to compare the psychological well-being of individuals with PWS and their caregivers, providing valuable insights that can potentially improve the quality of care for these individuals. The sample recruited at the Division of Auxology, IRCCS Istituto Auxologico Italiano, was composed of 30 adult subjects with PWS (11 men and 19 women; mean age ± SD: 36.4 ± 10.31 years; mean Body Mass Index (BMI): 35.7 ± 8.92: kg/m2) and their caregivers (10 men and 20 women). To assess the psychological condition of caregivers, the Italian-validated versions of the Depression Anxiety and Stress Scale (DASS-21) and the Coping Orientation to the Problems Experiences (COPE) were used, while to assess the psychological well-being of individuals with PWS and their caregivers, the Italian validated version of the Psychological General Well-Being Index (PGWBI) was used. Results Depression (p

Abstract Background The parasagittal dura, a tissue that lines the walls of the superior sagittal sinus, acts as an active site for immune-surveillance, promotes the reabsorption of cerebrospinal fluid, and facilitates the removal of metabolic waste products from the brain. Cerebrospinal fluid is important for the distribution of growth factors that signal immature neurons to proliferate and migrate. Autism spectrum disorder is characterized by altered cerebrospinal fluid dynamics. Methods In this retrospective study, we investigated potential correlations between parasagittal dura volume, brain structure volumes, and clinical severity scales in young children with autism spectrum disorder. We employed a semi-supervised two step pipeline to extract parasagittal dura volume from 3D-T2 Fluid Attenuated Inversion Recovery sequences, based on U-Net followed by manual refinement of the extracted parasagittal dura masks. Results Here we show that the parasagittal dura volume does not change with age but is significantly correlated with cerebrospinal fluid (p-value = 0.002), extra-axial cerebrospinal fluid volume (p-value = 0.0003) and severity of developmental delay (p-value = 0.024). Conclusions These findings suggest that autism spectrum disorder children with severe developmental delay may have a maldeveloped parasagittal dura that potentially perturbs cerebrospinal fluid dynamics.

Abstract Quantum Hall systems are platforms of choice to study topological properties of condensed matter systems and anyonic exchange statistics. In this work we have developed a tunable radiofrequency edge magnetoplasmonic resonator controlled by both the magnetic field and a set of electrostatic gates, meant to serve as a versatile platform for future interferometric devices designed to evidence non-abelian anyons. In our device, gates allow us to change both the size of the resonant cavity and the electronic density of the two-dimensional electron gas. We show that we can continuously control the frequency response of our resonator, making it possible to develop an edge magnetoplasmon interferometer. As we reach smaller sizes of our resonator, finite size effects caused by the measurement probes manifest. In the future, such device will be a valuable tool to investigate the properties of non-abelian anyons in the fractional quantum Hall regime.

Abstract Background Eating disorders (EDs) pose a significant risk to health, especially when not diagnosed early. For several years EDs and oral health has been extensively studied, and now it is quite clear the existence of a correlation between specific oral manifestations and these disorders. While these oral signs could potentially aid early diagnosis of EDs, their identification and the eventual establishment of a correlation is currently heavily limited to the clinician’s experience. The present systematic review critically examines existing literature, offering an updated overview of oro-dental manifestations associated with EDs. Method MEDLINE (via PubMed), Web of Science, Scopus, and grey literature were searched, and relevant epidemiological comparative studies were screened using the Rayyan software. No limitations have been imposed on the research regarding oro-dental outcomes, encompassing all medically diagnosed EDs. The quality of the studies was valuated using AXIS appraisal tool for cross-sectional studies. Result Out of 3990 studies, 32 fulfilled the eligibility criteria and were included in the synthesis. The identified eating disorders include Anorexia Nervosa, Bulimia Nervosa and/or Eating Disorders Not Otherwise Specified, predominantly among female subjects, primarily originating from Europe. The evaluated oro-dental outcomes include dental erosion, caries, saliva assessment, hygiene-periodontal parameters, and mucosal tissue appearance. The association with erosion is confirmed while gingival recession, dentinal hypersensitivity, salivary flow thresholds and aspects relating to oral pathology are receiving increasing support from emerging evidence. Discussion This trend emphasizes the critical role of the complete intraoral examination to detect significant oro-dental signs that may indicate the onset of an ED.

Abstract We aimed to assess diagnostic accuracy of plasma p-tau181 and NfL separately and in combination in discriminating Subjective Cognitive Decline (SCD) and Mild Cognitive Impairment (MCI) patients carrying Alzheimer’s Disease (AD) pathology from non-carriers; to propose a flowchart for the interpretation of the results of plasma p-tau181 and NfL. We included 43 SCD, 41 MCI and 21 AD-demented (AD-d) patients, who underwent plasma p-tau181 and NfL analysis. Twenty-eight SCD, 41 MCI and 21 AD-d patients underwent CSF biomarkers analysis (Aβ1-42, Aβ1-42/1–40, p-tau, t-tau) and were classified as carriers of AD pathology (AP+) it they were A+/T+ , or non-carriers (AP−) when they were A−, A+/T−/N−, or A+/T−/N+ according to the A/T(N) system. Plasma p-tau181 and NfL separately showed a good accuracy (AUC = 0.88), while the combined model (NfL + p-tau181) showed an excellent accuracy (AUC = 0.92) in discriminating AP+ from AP− patients. Plasma p-tau181 and NfL results were moderately concordant (Coehn’s k = 0.50, p

Abstract In order to tackle the global increase in overweight and obesity prevalence, several nutrient profiling systems have been developed; among others, Food Compass Score (FCS) has been designed to encompass multiple domains of food healthfulness. However, environmental sustainability of healthy diets is another crucial dimension which should not be overlooked in the context of human health. The aim of the present study is to assess the association between healthiness and environmental sustainability of food items, using the FCS and Agribalyse databases, respectively. A total of 806 matching food items were identified, grouped in 12 food categories; within each category, differences in median Z-scores between FCS and Single Environmental Footprint (EF) Score were assessed. While Fruits, Legumes and Nuts, Mixed foods, Meat Poultry and Eggs (MPE), Savory and Sweets, and Vegetables showed statistically significant differences (all p

An accurate and complete taxonomic description of the diversity present in an environmental sample is out of reach at this time. Instead, metabarcoding is used today and it is expected that OTUs represent a category relevant for biodiversity inventories on a molecular basis. However, artefacts in the production of OTUs can occur at different stages and may impact ecological conclusions. We propose to evaluate the quality of OTUs in a sample by characterising the deviation of each OTU’s dissimilarity array from that of an ideal OTU where all sequences are at distances smaller than the barcoding gap. We consider two deviations: the creation of composed OTUs, corresponding to the artificial merging of several OTUs and the creation of noisy OTUs that contain some sequences that are loosely associated with the core sequence of the OTUs and that do not form a compact subgroup. We propose a simple and automatic 2-step method that successively categorises the OTUs of a sample as composed or single and then identifies OTUs with noise amongst the single ones. The associated code is available at https://forgemia.inra.fr/alain.franc/otu_shape. We applied the method on 32 samples of diatoms from Arcachon Bay (France) that represent contrasted environmental conditions and we obtained good agreement with expert categorisation of OTUs. We suggest that single OTUs without noise can be used as such for further ecological studies. Composed OTUs should be post-treated with classical clustering or community detection tools. The quality of single OTUs with noise remains to be further tested via supplementary studies on a diversity of organisms.

Abstract Therapy of melanoma has improved dramatically over the last years thanks to the development of targeted therapies (MAPKi) and immunotherapies. However, drug resistance continues to limit the efficacy of these therapies. Our research group has provided robust evidence as to the involvement of a set of microRNAs in the development of resistance to target therapy in BRAF-mutated melanomas. Among them, a pivotal role is played by the oncosuppressor miR-579-3p. Here we show that miR-579-3p and the microphthalmia-associated transcription factor (MITF) influence reciprocally their expression through positive feedback regulatory loops. In particular we show that miR-579-3p is specifically deregulated in BRAF-mutant melanomas and that its expression levels mirror those of MITF. Luciferase and ChIP studies show that MITF is a positive regulator of miR-579-3p, which is located in the intron 11 of the human gene ZFR (Zink-finger recombinase) and is co-transcribed with its host gene. Moreover, miR-579-3p, by targeting BRAF, is able to stabilize MITF protein thus inducing its own transcription. From biological points of view, early exposure to MAPKi or, alternatively miR-579-3p transfection, induce block of proliferation and trigger senescence programs in BRAF-mutant melanoma cells. Finally, the long-term development of resistance to MAPKi is able to select cells characterized by the loss of both miR-579-3p and MITF and the same down-regulation is also present in patients relapsing after treatments. Altogether these findings suggest that miR-579-3p/MITF interplay potentially governs the balance between proliferation, senescence and resistance to therapies in BRAF-mutant melanomas.

El trabajo argumenta que la organización religiosa que caracteriza a las religiones afroamericanas permite lograr transformaciones de identidades personales -obteniendo conversiones individuales que posibilitan su expansión - pero no resulta particularmente apropiado para construir identidades colectivas que permitan un accionar conjunto de los practicantes en beneficio de la comunidad religiosa. Utilizando perspectivas desarrolladas en el estudio de movimientos sociales, analiza el caso de las religiones afrobrasileñas en Argentina para mostrar cómo los líderes religiosos preocupados por la legitimación social de la religión deben desarrollar marcos colectivos de acción que impulsen la construcción de identidades colectivas. Para este fin, deben movilizar recursos económicos y simbólicos al interior y al exterior de su religión, así como aprovechar la cambiante estructura de oportunidades que les presenta el medio social en que se desenvuelven. La dificultad para crear una identidad colectiva resulta particularmente problemática para contrarrestar la estigmatización de la que son objeto en los nuevos contextos sociales a los cuales estas religiones se expanden

Abstract Extracellular vesicles (EVs), crucial mediators of cell‐to‐cell communication, hold significant diagnostic potential due to their ability to concentrate protein biomarkers in bodily fluids. However, challenges in isolating EVs from biological specimens hinder their widespread use. The preferred strategy involves direct analysis, integrating isolation and analysis solutions, with immunoaffinity methods currently dominating. Yet, the heterogeneous nature of EVs poses challenges, as proposed markers may not be as universally present as thought, raising concerns about biomarker screening reliability. This issue extends to EV‐mimics, where conventional methods may lack applicability. Addressing these challenges, the study reports on Membrane Sensing Peptides (MSP) as pan‐vesicular affinity ligands for both EVs and their non‐canonical analogs, streamlining capture and phenotyping through Single Molecule Array (SiMoA). MSP ligands enable direct analysis of circulating EVs, eliminating the need for prior isolation. Demonstrating clinical translation, MSP technology detects an EV‐associated epitope signature in serum and plasma, distinguishing myocardial infarction from stable angina. Additionally, MSP allow analysis of tetraspanin‐lacking Red Blood Cell‐derived EVs, overcoming limitations associated with antibody‐based methods. Overall, the work underlines the value of MSP as complementary tools to antibodies, advancing EV analysis for clinical diagnostics and beyond, and marking the first‐ever peptide‐based application in SiMoA technology.

IntroductionParents vary in their gradual adaptation to the demands of caring for an autistic child. Their experiences can be positive, negative, or a combination of both, depending on the severity of the cases and various personal and social factors. Cross-cultural comparisons can aid in understanding how contextual factors, such as the availability of social and health services, and cultural factors, such as family relationships and the distribution of care burden, may influence the caregiving experience. However, there is a limited amount of cross-cultural research on this topic, which is almost exclusively quantitative.Aims and methodsFrom an ecocultural perspective, our interview-based study aimed to explore the experiences of Australian (15) and Italian (11) parents of autistic children living in their respective countries.ResultsThe analysis identified three main themes. Life through autism, autism through life: coexisting with an unexpected life partner, Parenting autistic children: reorganization of parents’ subjectivity and familiar dynamics, and The unseen side of disability: autism communities between inclusion and segregation.DiscussionOur comparative approach reveals both commonalities and differences between the two groups of participants. The similarities support features previously identified in the literature: the emotional and physical burden on parents and the positive impact on parental identity. The differences relate to the diagnostic process, interactions with health professionals, the impact of autism on family dynamics and parental perspectives, and the role assigned to siblings. Despite facing similar challenges, these differences reveal how Italian and Australian parents articulate different understandings linked to social and cultural differences.

Summary: Tel1/ataxia telangiectasia mutated (ATM) kinase plays multiple functions in response to DNA damage, promoting checkpoint-mediated cell-cycle arrest and repair of broken DNA. In addition, Saccharomyces cerevisiae Tel1 stabilizes replication forks that arrest upon the treatment with the topoisomerase poison camptothecin (CPT). We discover that inactivation of the Exo1 nuclease exacerbates the sensitivity of Tel1-deficient cells to CPT and other agents that hamper DNA replication. Furthermore, cells lacking both Exo1 and Tel1 activities exhibit sustained checkpoint activation in the presence of CPT, indicating that Tel1 and Exo1 limit the activation of a Mec1-dependent checkpoint. The absence of Tel1 or its kinase activity enhances recombination between inverted DNA repeats induced by replication fork blockage in an Exo1-dependent manner. Thus, we propose that Exo1 processes intermediates arising at stalled forks in tel1 mutants to promote DNA replication recovery and cell survival.

Spinal cord injury (SCI) is a devastating condition that can cause significant motor and sensory impairment. Microglia, the central nervous system's immune sentinels, are known to be promising therapeutic targets in both SCI and neurodegenerative diseases. The most effective way to deliver medications and control microglial inflammation is through nanovectors; however, because of the variability in microglial morphology and the lack of standardized techniques, it is still difficult to precisely measure their activation in preclinical models. This problem is especially important in SCI, where the intricacy of the glia response following traumatic events necessitates the use of a sophisticated method to automatically discern between various microglial cell activation states that vary over time and space as the secondary injury progresses. We address this issue by proposing a deep learning-based technique for quantifying microglial activation following drug-loaded nanovector treatment in a preclinical SCI model. Our method uses a convolutional neural network to segment and classify microglia based on morphological characteristics. Our approach's accuracy and efficiency are demonstrated through evaluation on a collection of histology pictures from injured and intact spinal cords. This robust computational technique has potential for analyzing microglial activation across various neuropathologies and demonstrating the usefulness of nanovectors in modifying microglia in SCI and other neurological disorders. It has the ability to speed development in this crucial sector by providing a standardized and objective way to compare therapeutic options.

Reduction of amyloid beta (Aβ) has been shown to be effective in treating Alzheimer's disease (AD), but the underlying assumption that neurons are the main source of pathogenic Aβ is untested. Here, we challenge this prevailing belief by demonstrating that oligodendrocytes are an important source of Aβ in the human brain and play a key role in promoting abnormal neuronal hyperactivity in an AD knock-in mouse model. We show that selectively suppressing oligodendrocyte Aβ production improves AD brain pathology and restores neuronal function in the mouse model in vivo. Our findings suggest that targeting oligodendrocyte Aβ production could be a promising therapeutic strategy for treating AD.

IntroductionSemen cryopreservation is the most popular practice for semen production for artificial insemination and in vitro fertilization in cattle. The Seminal plasma contains extracellular vesicles (spEVs) which modulate sperm viability and function during oocyte fecundation. The study of spEVs in frozen-thawed semen doses may yield novel indicators for predicting bull fertility, but the presence of the semen extender may hinder molecular profiling of spEVs. The aim of this study was to provide extensive characterization of EVs isolated from seminal plasma before and after the cryopreservation process and the addition of a commercial animal protein-free semen extender to understand the potential influence of EVs originating from the extender in hindering the use of spEVs derived biomarkers for assessment of bull fertility.MethodsEVs were isolated from the seminal plasma (with or without the extender), from the cryopreserved straw devoid of spermatozoa, and from the extender using two different methods, ultracentrifugation (UC) and size exclusion chromatography (SEC), and characterized for their structure and composition.ResultsPhysical characterization of EVs showed that size and particle numbers were related to the method of isolation. spEVs were larger but less abundant (UC: 168.9 nm, n = 2.68 × 109; SEC: 197.0 nm, n = 6.42 × 109) compared to extender EVs (UC: 129.0 nm, n = 2.68 × 1011; SEC: 161.8 nm, n = 6.47 × 1011). Western blotting analysis (WB) confirmed the presence of typical EV markers in spEVS: the membrane bound CD9 (25 kDa) and the luminal markers Alix (96 kDa) and TSG101 (48 KDa). Although Transmission Electron Microscopy confirmed the presence of a lipid bilayer structure in all preparations, no specific EV markers were detected in the vesicles isolated from extender when the Single Molecule Array (SiMoa) was used. A total of 724 Bos taurus miRNAs were identified in at least one preparation. The percentage of miRNAs identified in EVs from the extender (0.05%−0.49% of the total reads) was lower than in the preparation containing spEVs (10.56%–63.69% of the total reads). Edge-R identified a total of 111 DE-miRNAs between EVs isolated from the extender by two methods. Among them, 11 DE-miRNAs (bta-miR-11980, bta-miR-11987, bta-miR-12057, bta-miR-1246, bta-miR-125b, bta-miR-181b, bta-miR-2340, bta-miR-2358, bta-miR-2478, bta-miR-2898, and bta-miR-345-3p) were also abundant in EVs isolated from seminal plasma preparations with extender.ConclusionThis study clearly demonstrates that the presence of the extender does not prevent the characterization of spEVs in cryopreserved semen. However, the molecular profiling of spEVs can be influenced by the isolation method used and by the presence of some miRNAs from the extender. Therefore, in such studies, it is advisable to characterize both spEVs and the vesicles isolated from the extender.

The authentication process involves all the supply chain stakeholders, and it is also adopted to verify food quality and safety. Food authentication tools are an essential part of traceability systems as they provide information on the credibility of origin, species/variety identity, geographical provenance, production entity. Moreover, these systems are useful to evaluate the effect of transformation processes, conservation strategies and the reliability of packaging and distribution flows on food quality and safety. In this manuscript, we identified the innovative characteristics of food authentication systems to respond to market challenges, such as the simplification, the high sensitivity, and the non-destructive ability during authentication procedures. We also discussed the potential of the current identification systems based on molecular markers (chemical, biochemical, genetic) and the effectiveness of new technologies with reference to the miniaturized systems offered by nanotechnologies, and computer vision systems linked to artificial intelligence processes. This overview emphasizes the importance of convergent technologies in food authentication, to support molecular markers with the technological innovation offered by emerging technologies derived from biotechnologies and informatics. The potential of these strategies was evaluated on real examples of high-value food products. Technological innovation can therefore strengthen the system of molecular markers to meet the current market needs; however, food production processes are in profound evolution. The food 3D-printing and the introduction of new raw materials open new challenges for food authentication and this will require both an update of the current regulatory framework, as well as the development and adoption of new analytical systems.

Abstract Background Degeneration of the locus coeruleus (LC) noradrenergic system contributes to clinical symptoms in Alzheimer’s disease (AD) and Parkinson’s disease (PD). Diffusion magnetic resonance imaging (MRI) has the potential to evaluate the integrity of the LC noradrenergic system. The aim of the current study was to determine whether the diffusion MRI-measured integrity of the LC and its tracts are sensitive to noradrenergic degeneration in AD and PD. Methods Post-mortem in situ T1-weighted and multi-shell diffusion MRI was performed for 9 AD, 14 PD, and 8 control brain donors. Fractional anisotropy (FA) and mean diffusivity were derived from the LC, and from tracts between the LC and the anterior cingulate cortex, the dorsolateral prefrontal cortex (DLPFC), the primary motor cortex (M1) or the hippocampus. Brain tissue sections of the LC and cortical regions were obtained and immunostained for dopamine-beta hydroxylase (DBH) to quantify noradrenergic cell density and fiber load. Group comparisons and correlations between outcome measures were performed using linear regression and partial correlations. Results The AD and PD cases showed loss of LC noradrenergic cells and fibers. In the cortex, the AD cases showed increased DBH + immunoreactivity in the DLPFC compared to PD cases and controls, while PD cases showed reduced DBH + immunoreactivity in the M1 compared to controls. Higher FA within the LC was found for AD, which was correlated with loss of noradrenergic cells and fibers in the LC. Increased FA of the LC-DLPFC tract was correlated with LC noradrenergic fiber loss in the combined AD and control group, whereas the increased FA of the LC-M1 tract was correlated with LC noradrenergic neuronal loss in the combined PD and control group. The tract alterations were not correlated with cortical DBH + immunoreactivity. Conclusions In AD and PD, the diffusion MRI-detected alterations within the LC and its tracts to the DLPFC and the M1 were associated with local noradrenergic neuronal loss within the LC, rather than noradrenergic changes in the cortex.

This work presents the new model called CRHyME (Climatic Rainfall Hydrogeological Modelling Experiment), a tool for geo-hydrological hazard evaluation. CRHyME is a physically based and spatially distributed model written in the Python language that represents an extension of the classic hydrological models working at the basin scale. CRHyME's main focus consists of simulating rainfall-induced geo-hydrological instabilities such as shallow landslides, debris flows, catchment erosion and sediment transport into a river. These phenomena are conventionally decoupled from a hydrological routine, while in CRHyME they are simultaneously and quantitatively evaluated within the same code through a multi-hazard approach. CRHyME is applied within some case studies across northern Italy. Among these, the Caldone catchment, a well-monitored basin of 27 km2 located near the city of Lecco (Lombardy), was considered for the calibration of solid-transport routine testing, as well as the spatial-scale dependence related to digital terrain resolution. CRHyME was applied across larger basins of the Valtellina (Alps) and Emilia (Apennines) areas (∼2600 km2) which have experienced severe geo-hydrological episodes triggered by heavy precipitation in the recent past. CRHyME's validation has been assessed through NSE (Nash–Sutcliffe efficiency) and RMSE (root mean square error) hydrological-error metrics, while for landslides the ROC (receiver operating characteristic) methodology was applied. CRHyME has been able to reconstruct the river discharge at the reference hydrometric stations located at the outlets of the basins to estimate the sediment yield at some hydropower reservoirs chosen as a reference and to individuate the location and the triggering conditions of shallow landslides and debris flows. The good performance of CRHyME was reached, assuring the stability of the code and a rather fast computation and maintaining the numerical conservativity of water and sediment balances. CRHyME has shown itself to be a suitable tool for the quantification of the geo-hydrological process and thus useful for civil-protection multi-hazard assessment.

Abstract Regional differences in synaptic degeneration may underlie differences in clinical presentation and neuropathological disease progression in Parkinson’s Disease (PD) and Dementia with Lewy bodies (DLB). Here, we mapped and quantified synaptic degeneration in cortical brain regions in PD, PD with dementia (PDD) and DLB, and assessed whether regional differences in synaptic loss are linked to axonal degeneration and neuropathological burden. We included a total of 47 brain donors, 9 PD, 12 PDD, 6 DLB and 20 non-neurological controls. Synaptophysin+ and SV2A+ puncta were quantified in eight cortical regions using a high throughput microscopy approach. Neurofilament light chain (NfL) immunoreactivity, Lewy body (LB) density, phosphorylated-tau and amyloid-β load were also quantified. Group differences in synaptic density, and associations with neuropathological markers and Clinical Dementia Rating (CDR) scores, were investigated using linear mixed models. We found significantly decreased synaptophysin and SV2A densities in the cortex of PD, PDD and DLB cases compared to controls. Specifically, synaptic density was decreased in cortical regions affected at Braak α-synuclein stage 5 in PD (middle temporal gyrus, anterior cingulate and insula), and was additionally decreased in cortical regions affected at Braak α-synuclein stage 4 in PDD and DLB compared to controls (entorhinal cortex, parahippocampal gyrus and fusiform gyrus). Synaptic loss associated with higher NfL immunoreactivity and LB density. Global synaptophysin loss associated with longer disease duration and higher CDR scores. Synaptic neurodegeneration occurred in temporal, cingulate and insular cortices in PD, as well as in parahippocampal regions in PDD and DLB. In addition, synaptic loss was linked to axonal damage and severe α-synuclein burden. These results, together with the association between synaptic loss and disease progression and cognitive impairment, indicate that regional synaptic loss may underlie clinical differences between PD and PDD/DLB. Our results might provide useful information for the interpretation of synaptic biomarkers in vivo.

In this work we theoretically investigate the possibility of observing strong coupling at mid-infrared frequencies within the group-IV semiconductor material platform. Our results show that the strong coupling condition is attainable in Ge/SiGe quantum wells integrated in hybrid metal-semiconductor microcavities, featuring a highly n-doped SiGe layer as one of the mirrors.

This study reports the experimental demonstration of the first waveguide-integrated SiGe modulator using a PIN diode operating in a wide spectral range of the mid-infrared region. At the wavelength of 10 µm, an extinction ratio up to 10 dB is obtained in injection regime and 3.2 dB in depletion regime. High speed operation is obtained, up to 1.5 GHz. Furthermore, the device can also operate as an integrated photodetector. Photodetection has thus been characterized from 5.2 µm to 10 µm wavelengths showing an internal responsivity around 1 mA/W, and a 3 dB electro-optical bandwidth of 32 MHz. These results show a significant advancement in integrated photodetectors and electro-optical modulators for mid-infrared spectroscopy.

Abstract In models with spontaneous symmetry breaking by scalar fields in large group representations, we observe that some of the scalar masses can be loop-suppressed with respect to the naive expectation from symmetry selection rules. We present minimal models — the SU(2) five-plet and SU(3) ten-plet — with such accidentally light scalars, featuring compact tree-level flat directions lifted by radiative corrections. We sketch some potential applications, from stable relics and slow roll in cosmology, to hierarchy and fine-tuning problems in particle physics.

Waste material classification is critical for efficient recycling and waste management. This study proposes a novel, low-cost material classification system based on a single, voltage-tunable Ge-on-Si photodetector operating across the visible and short-wave infrared (SWIR) spectral regions. Thanks to its tunability, the sensor is able to extract spectral information, and the system effectively distinguishes between seven different materials, including plastics, aluminum, glass, and paper. The system operates with a broadband illuminator, and material identification is obtained through the processing of the photocurrent signal at different bias voltages with classification algorithms. Here, we demonstrate the basic system functionality and near real-time classification of different waste materials.

Invasive alien plants represent one of the five major threats to biodiversity and the disruption of ecosystems. They are introduced through various routes, starting with commercial trade. Preventing their introduction is essential to avoid the spread of new invasive plants. In this paper, we propose a new early warning DNA barcoding tool for invasive plant detection. Eight invasive alien species of European Union concern (i.e., Ludwigia grandiflora, Elodea nuttallii, Myriophyllum aquaticum, Pontederia crassipes, Ailanthus altissima, Heracleum mantegazzianum, Impatiens glandulifera, Pueraria montana) were selected and analysed. A unique DNA marker for each species was identified and amplified using species-specific primers capable of identifying the presence of alien species. To verify whether the approach could detect the presence of alien plants in urban areas from lawn clippings, mixes with typical urban spontaneous plants and invasive species were tested. In all mixes, only the invasive species was identified. This rapid detection capability will enable environmental operators to intervene promptly to contain the spread of invasive plants before they can cause significant damage to the local ecosystem. This tool could have a significant impact on the protection of local biodiversity and the integrity of urban habitats.

Antecedentes: El proceso de prescripción de medicamentos debe explicar riesgos, beneficios y alternativas. Objetivo: Realizar un análisis bioético sobre conocimiento de hormonoterapia. Método: Estudio transversal, 37 entrevistas. Resultados: El 59.5% decía saber por qué tomaba hormonoterapia. Solamente el 24.3% contestó el verdadero motivo. El 35.1% alguna vez suspendió el tratamiento. No hubo significancia estadística al realizar prueba de Fisher en apego al tratamiento y conocimiento del motivo por el cual tomaban hormonoterapia. Discusión: La adherencia al tratamiento hormonal en mexicanas disminuye un 30.5% en cinco años. La mayoría de las pacientes no tienen el conocimiento del por qué toman la hormonoterapia. Las principales causas del apego incorrecto al tratamiento son por falta de medicamentos en la institución y la desinformación percibida por el paciente. Ambas causas son solucionables. Conclusión: Los pacientes con información correcta mejoran su autonomía para tomar decisiones y el adecuado uso al tratamiento indicado por el especialista.

Background: The current systematic review and meta-analysis aims to synthesize findings from Italian studies that have investigated emotional and behavioural problems in clinical and at-risk samples of adolescents, as assessed by the Achenbach System of Empirically Based Assessment (ASEBA) instruments, including Child Behaviour Checklist (CBCL), the self-report Youth Self Report (YSR) and the teacher-report Teacher Report Form (TRF). It also investigates possible effects of gender, age, and time of assessment (pre-post COVID-19 pandemic), and their link with other psychological factors. Methods: The latest PRISMA guidelines were followed, and this study was registered in PROSPERO (CRD42022299999). Scopus, EBSCO, PubMed, Web of Sciences, and ProQuest databases were used considering the time frame from January 2001 to November 2021. Two blinded investigators remove duplicates and double screened 7103 records. They selected and extract information from 40 eligible studies, which were also evaluated through the Newcastle-Ottawa Scale. Results: Overall, emotional-behavioural problems were mainly investigated through the CBCL 6-18 both in clinical samples (N = 2244), mostly composed of adolescents with a diagnosis of eating disorders and externalized disorders, and at-risk samples (N = 868), mostly of adolescents with a medical condition. As expected, adolescents from clinical samples had higher scores on the ASEBA scales than their peers belonging to the at-risk samples. No effect related to gender, time of assessment and study quality on emotional behavioural problems emerged. However, a significant effect of age was found in clinical samples, specifically a decrease in externalizing symptoms with the increase of age. Lastly, emotional-behavioural problems were mainly investigated in association with emotional regulation difficulties both in clinical and at-risk samples. Conclusions: For the first time, meta-analytic data on rates of emotional-behavioral problems in Italian clinical and at-risk adolescents are provided. Implications include the need of more data, especially with the TRF and from Centre e Southern Italy, to solve doubts emerged about the absence of moderators. The authors discuss limitations related to the heterogeneity of the studies, suggesting future research directions.

Individual differences in aggressiveness, if consistent across time and contexts, may contribute to the long-term maintenance of social hierarchies in complex animal societies. Although agonistic interactions have previously been used to calculate individuals’ positions within a dominance hierarchy, to date the repeatability of agonistic behaviour has not been tested when calculating social rank. Here, we examined the consistency and social relevance of aggressiveness as a personality trait in a free-flying population of greylag geese (Anser anser). For each individual, we quantified (i) aggressiveness using a standardized mirror stimulation test and (ii) dominance ranking based on the number of agonistic interactions won and lost in a feeding context. We found that individual differences in aggressiveness were significantly repeatable and that individuals’ aggressiveness predicted their dominance rank position. The flock showed a robust and intermediately steep dominance hierarchy. Social rank was higher in paired birds, males and older birds, and most agonistic interactions occurred between individuals with moderate rank differences. We suggest that selection favours aggressiveness as a personality trait associated with resource acquisition and social rank, whereby a dominance hierarchy may increase the benefits of group living and reduce costs over conflict within dyads.

Abstract Background BRAF-mutant melanoma patients benefit from the combinatorial treatments with BRAF and MEK inhibitors. However, acquired drug resistance strongly limits the efficacy of these targeted therapies in time. Recently, many findings have underscored the involvement of microRNAs as main drivers of drug resistance. In this context, we previously identified a subset of oncomiRs strongly up-regulated in drug-resistant melanomas. In this work, we shed light on the molecular role of two as yet poorly characterized oncomiRs, miR-4443 and miR-4488. Methods Invasion and migration have been determined by wound healing, transwell migration/invasion assays and Real Time Cell Analysis (RTCA) technology. miR-4488 and miR-4443 have been measured by qRT-PCR. Nestin levels have been tested by western blot, confocal immunofluorescence, immunohistochemical and flow cytometry analyses. Results We demonstrate that the two oncomiRs are responsible for the enhanced migratory and invasive phenotypes, that are a hallmark of drug resistant melanoma cells. Moreover, miR-4443 and miR-4488 promote an aberrant cytoskeletal reorganization witnessed by the increased number of stress fibers and cellular protrusions-like cancer cell invadopodia. Mechanistically, we identified the intermediate filament nestin as a molecular target of both oncomiRs. Finally, we have shown that nestin levels are able to predict response to treatments in melanoma patients. Conclusions Altogether these findings have profound translational implications in the attempt i) to develop miRNA-targeting therapies to mitigate the metastatic phenotypes of BRAF-mutant melanomas and ii) to identify novel biomarkers able to guide clinical decisions. Graphical Abstract

Abstract Purpose The aim of the study was to examine the effects of meal supervision, provided by health professionals, volunteers or family members, on anthropometric, nutritional, psychological, and behavioural outcomes in patients with eating disorders (EDs). Methods The present systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The last search was conducted in three databases (PubMed, Scopus, and the Cochrane library). Inclusion criteria considered paediatric and adult patients suffering from EDs, regardless of ethnicity, and treated in different therapeutic settings. The quality of the studies was evaluated using the Newcastle Ottawa Scale (NOS) adapted for cross-sectional studies and Version 2 of the Cochrane risk-of-bias assessment tool for randomised trials. Results 3282 articles were retrieved, out of which only 6 met the eligibility criteria. A marked heterogeneity in definitions and approaches to supervised mealtime was observed. This variability emerged in the methodologies used in the supervised meal, and in the reference values for the outcome measures that were used, such as the analysis of different parameters. Based on these observations, mealtime assistance provided to patients with EDs shows an overall positive effect on eating behaviour and dysfunctional attitudes. Future research should be prompted to provide a thorough definition of a structured procedure for meal assistance to be potentially and systematically included in the nutritional rehabilitation protocols for patients with EDs. Level of evidence Level IV systematic reviews of uncontrolled trials.

Vaginal vault prolapse is one of the main reasons for reoperation in patients with pelvic organ prolapse. Effective correction of the vaginal apex is essential for lasting repair for these women. Apical suspension of the sacrospinous ligament is probably one of the main vaginal treatments still offered to patients today. We proposed an evaluation of the functional and anatomical results of long-term sacrospinous ligament fixation. Objective: The purpose of this study was to evaluate the 10-year results of sacrospinous ligament suspension as primary repair for apical prolapse and to evaluate long-term side effects. Materials and Methods: A retrospective study analyzed 10-year follow-up after prolapse repair using sacrospinous ligament suspension. A subjective recurrence was identified as the postoperative occurrence of swelling symptoms based on a particular item on the Italian Prolapse Quality of Life (P-QoL) questionnaire. An objective recurrence was defined as a postoperative decline to stage II or below in any compartment based on the POP-Q system or the requirement for additional surgery. The assessment of postoperative subjective satisfaction was conducted using the Patient Global Impression of Improvement (PGI-I) score. Results: In total, 40 patients underwent sacrospinous ligament fixation. Objective recurrence was remarkably high, as it was observed in 17 (56.7%) patients. Subjective recurrence was reported by ten (33.3%) women, and reintervention occurred in two (6.7%) of patients. From the point of view of quality of life, according to the PGI-I, twenty-three (76.7%) patients described some degree of improvement after surgery, four (13.3%) described their status as unmodified, and three (10%) reported some form of worsening after primary treatment. Conclusions: Transvaginal repair with sacrospinous fixation is a long-lasting option for prolapse repair, with improvement in every POP-q parameter. Some degree of anterior recurrence, recurrence of symptoms with swelling, or an overall worsening of quality of life after surgery is possible.

Abstract Background Per-/polyfluoroalkyl substances (PFASs) are persistent organic pollutants and suspected endocrine disruptors. Objective The aim of this work was to conduct a systematic review with meta-analysis to summarise the associations between prenatal or childhood exposure to PFASs and childhood overweight/obesity. Methods The search was performed on the bibliographic databases PubMed and Embase with text strings containing terms related to prenatal, breastfeeding, childhood, overweight, obesity, and PFASs. Only papers describing a biomonitoring study in pregnant women or in children up to 18 years that assessed body mass index (BMI), waist circumference (WC), or fat mass in children were included. When the estimates of the association between a PFAS and an outcome were reported from at least 3 studies, a meta-analysis was conducted; moreover, to correctly compare the studies, we developed a method to convert the different effect estimates and made them comparable each other. Meta-analyses were performed also stratifying by sex and age, and sensitivity analyses were also performed. Results In total, 484 and 779 articles were retrieved from PubMed and Embase, respectively, resulting in a total of 826 articles after merging duplicates. The papers included in this systematic review were 49: 26 evaluating prenatal exposure to PFASs, 17 childhood exposure, and 6 both. Considering a qualitative evaluation, results were conflicting, with positive, negative, and null associations. 30 papers were included in meta-analyses (19 prenatal, 7 children, and 4 both). Positive associations were evidenced between prenatal PFNA and BMI, between PFOA and BMI in children who were more than 3 years, and between prenatal PFNA and WC. Negative associations were found between prenatal PFOS and BMI in children who were 3 or less years, and between PFHxS and risk of overweight. Relatively more consistent negative associations were evidenced between childhood exposure to three PFASs (PFOA, PFOS, and PFNA) and BMI, in particular PFOS in boys. However, heterogeneity among studies was high. Conclusion Even though heterogeneous across studies, the pooled evidence suggests possible associations, mostly positive, between prenatal exposure to some PFASs and childhood BMI/WC; and relatively stronger evidence for negative associations between childhood exposure to PFASs and childhood BMI.

Felice Alfonso Nava,1 Alessandra Mangia,2 Marco Riglietta,3 Lorenzo Somaini,4 Francesco Giuseppe Foschi,5 Ernesto Claar,6 Ivana Maida,7 Claudio Ucciferri,8 Francesca Frigerio,9 Candido Hernandez,10 Melania Dovizio,11 Valentina Perrone,11 Luca Degli Esposti,11 Massimo Puoti12 1U.O. Sanità Penitenziaria e Area Dipendenze, Azienda ULSS 6 Euganea, Padova, Italy; 2UOS Epatologia, Istituto di Ricovero e Cura “Casa Sollievo della Sofferenza”, S. Giovanni Rotondo, Italy; 3UOC Dipendenze, ASST Papa Giovanni XXIII, Bergamo, Italy; 4Servizio per le Dipendenze, SERT di Cossato, Biella, Italy; 5UOC Medicina Interna, Ospedale di Faenza, Faenza, Italy; 6UOC Medicina Interna, Ospedale Evangelico “Villa Betania”, Napoli, Italy; 7UOC Malattie Infettive e Parassitarie, Azienda Ospedaliero Universitaria di Sassari, Sassari, Italy; 8Clinica di Malattie Infettive Ospedale “SS Annunziata”, Chieti, Italy; 9Gilead Sciences, Milano, Italy; 10Gilead Sciences, Global Medical Affairs, Stockley Park, London, UB11 1BD, UK; 11CliCon S.R.L. Società Benefit, Health Economics and Outcomes Research, Bologna, Italy; 12SC Malattie Infettive, ASST Grande Ospedale Metropolitano Niguarda, Milano, ItalyCorrespondence: Luca Degli Esposti, CliCon S.r.l. Società Benefit, Health, Economics & Outcomes Research, Via Murri, 9, Bologna, 40137, Italy, Tel +39 544 38393, Fax +39 544 212699, Email luca.degliesposti@clicon.itPurpose: Hepatitis C virus (HCV) spreads from contact with blood of an infected person. HCV infections are common among people who use drugs (PWUDs), when sharing needles, syringes, or other equipment for injected drugs. The advent of pangenotypic direct-antiviral agents (DAA) in 2017 transformed the treatment landscape for HCV, but PWUDs remain a complex and hard-to-treat population with high risk of HCV reinfection. The aim of this real-world analysis was to characterize the demographic and clinical features of PWUDs in Italy, also focusing on comorbidity profile, treatment with DAAs, resource consumptions for the National Health System (NHS).Patients and Methods: During 01/2011– 06/2020, administrative databases of Italian healthcare entities, covering 3,900,000 individuals, were browsed to identify PWUDs with or without HCV infection. Among HCV+ patients, a further stratification was made into treated and untreated with DAAs. The date of PWUD or HCV first diagnosis or DAA first prescription was considered as index-date. Patients were then followed-up for one year. Alcohol-dependency was also investigated.Results: Total 3690 PWUDs were included, of whom 1141 (30.9%) PWUD-HCV+ and 2549 (69.1%) PWUD-HCV-. HCV-positive were significantly older (43.6 vs 38.5 years, p < 0.001), had a worse comorbidity profile (Charlson-index: 0.8 vs 0.4, p < 0.001), and high rates of psychiatric, respiratory, dermatological, musculoskeletal diseases and genitourinary (sexually transmitted) infections. Moreover, they received more drug prescriptions (other than DAAs, like anti-acids, antiepileptics, psycholeptics) and had undergone more frequent hospitalization, predominantly for hepatobiliary, respiratory system and mental disorders. DDA-untreated had significantly higher Charlson-index than DAA-treated (0.9 vs 0.6, p = 0.003). Alcoholism was found in 436 (11.8%) cases.Conclusion: This Italian real-world analysis suggests that PWUDs with HCV infection, especially those untreated with DAAs, show an elevated drug consumption due to their complex clinical profile. These findings could help to ameliorate the healthcare interventions on PWUDs with HCV infection.Keywords: drug abuse, hepatitis C virus, alcohol dependency, real-world evidence

Abstract Mammographic breast cancer screening is effective in reducing breast cancer mortality. Nevertheless, several limitations are known. Therefore, developing an alternative or complementary non-invasive tool capable of increasing the accuracy of the screening process is highly desirable. The objective of this study was to identify circulating microRNA (miRs) ratios associated with BC in women attending mammography screening. A nested case–control study was conducted within the ANDROMEDA cohort (women of age 46–67 attending BC screening). Pre-diagnostic plasma samples, information on life-styles and common BC risk factors were collected. Small-RNA sequencing was carried out on plasma samples from 65 cases and 66 controls. miR ratios associated with BC were selected by two-sample Wilcoxon test and lasso logistic regression. Subsequent assessment by RT-qPCR of the miRs contained in the selected miR ratios was carried out as a platform validation. To identify the most promising biomarkers, penalised logistic regression was further applied to candidate miR ratios alone, or in combination with non-molecular factors. Small-RNA sequencing yielded 20 candidate miR ratios associated with BC, which were further assessed by RT-qPCR. In the resulting model, penalised logistic regression selected seven miR ratios (miR-199a-3p_let-7a-5p, miR-26b-5p_miR-142-5p, let-7b-5p_miR-19b-3p, miR-101-3p_miR-19b-3p, miR-93-5p_miR-19b-3p, let-7a-5p_miR-22-3p and miR-21-5p_miR-23a-3p), together with body mass index (BMI), menopausal status (MS), the interaction term BMI * MS, life-style score and breast density. The ROC AUC of the model was 0.79 with a sensitivity and specificity of 71.9% and 76.6%, respectively. We identified biomarkers potentially useful for BC screening measured through a widespread and low-cost technique. This is the first study reporting circulating miRs for BC detection in a screening setting. Validation in a wider sample is warranted. Trial registration: The Andromeda prospective cohort study protocol was retrospectively registered on 27-11-2015 (NCT02618538).

Marta Barba,1 Alice Cola,2 Clarissa Costa,1 Antonio Liberatore,3 Matteo Frigerio2 1Obstetric and Gynecology Department - University of Milano-Bicocca, Monza, Italy; 2Gynecology Department, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy; 3School of Medicine, University of Milano-Bicocca, Monza, ItalyCorrespondence: Marta Barba, University of Milano-Bicocca, Via Pergolesi, 33, Monza, Italy, Tel +39 233 9434, Email m.barba8792@gmail.comObjective: Single-incision slings (SISs) are not considered the first surgical choice for stress urinary incontinence due to few data about long-term results. Our aim was to evaluate the outcomes of SISs 12 years after implantation and to search for consequences such as deterioration after a certain amount of time.Methods: We included women with stress urinary incontinence both clinically and urodynamically proven who underwent SISs procedure. Objective and subjective cure rates were compared to short-term outcomes to detect possible deterioration over time.Results: A total of 85 patients were analysed with a median follow-up of 12.0 (IQR 10.4– 12.8) years. Objective and subjective cure rates were 81.0% and 82.1%, respectively. Median (IQR) PGI-I scores and ICIQ-SF, respectively, were 1 (1– 2) and 0 (0– 6.8). No significant deterioration of outcomes over time was shown after comparison between short-term and long-term follow-ups (objective cure rate 84.5% vs 81.0%, p=0.684; subjective cure rates 92.9% vs 82.1%, p=0.060). Also, voiding symptoms and overactive bladder did not differ over time (20.2% vs 21.4%, p=1.000; 20.2% vs 33.3%, p=0.080, respectively).Conclusion: SISs were shown to be a procedure with a great efficacy and safety profile at very long-term follow-up.Keywords: complications, functional outcomes, long-term follow-up, quality of life, single-incision sling, stress urinary incontinence

BackgroundExperiences of stressful life events during transition may have a negative impact on quality of life (QoL) in trans persons. Little attention has been paid to this population in Switzerland, resulting in sparse data on their QoL and associated social factors.Methods30 participants were recruited during their medical transition treatment and surveyed on their experiences within this time period (13 months after the first medical intervention on average). After performing a diagnostic interview to evaluate their mental health, health-related QoL, psychological distress, self-esteem and the impact of life events that occurred in the last six months on participants were further assessed.ResultsApproximately 17% of participants had suffered from major depression, 43% reported having had suicidal thoughts or having attempted suicide, and 43% suffered from an anxiety disorder. Psychological distress was twice as high compared to the norm values of the cis population. With regard to QoL, trans individuals showed impairments in the mental domain. Stressful life events were particularly evident on a psychological and social level. Analysis showed a negative correlation between impact of life events and mental QoL and between psychological distress and mental QoL. At the same time, there was a positive correlation between self-esteem and mental QoL. Psychological distress and self-esteem emerged as independent significant predictors of mental QoL.ConclusionThis study shows lowered mental QoL and associations of low mental QoL with psychological distress, low self-esteem and stressful life events in trans individuals in Switzerland. The findings concur with the Gender Minority Stress Model and point out that medical transition must not be viewed in isolation but must be embedded in the framework of integrative psychosocial support.

BackgroundThis is a systematic review and meta-analysis of emotional and behavioral problems among Italian community adolescents in the last 20 years, as assessed through the ASEBA questionnaires CBCL 6–18, YSR 11–18 and TRF 6–18. Research questions address: (1) pooled means of problems’ scores in questionnaires scales; (2–3) variations in scores according to sociodemographic and time-related factors, and studies’ quality; (4) trends in research with ASEBA instruments along with other outcomes, e.g., psychopathological symptoms.MethodsA systematic literature review of Scopus, EBSCO, PubMed, Web of Science, and ProQuest databases using the PRISMA 2020 guidelines was conducted on November, 2021, and of grey literature on December, 2021. The quality of studies was assessed through the Newcastle-Ottawa Scale.ResultsForty-four studies were eligible for the systematic review, of which 34 were included for meta-analysis. Results showed that: (1) emotional-behavioral problems were higher when assessed by the CBCL and lower when assessed by the YSR compared to normative data; (2) there were no gender and age differences, except for higher scores of Anxious/Depression symptoms, in girls. (3) internalizing and attention problems increased over the last two decades. (4) major trends of Italian research investigate adolescents’ emotional behavioral problems concerning attachment, comorbid symptoms, especially internet addictions, and eating disorders.DiscussionDespite some limitations (e.g., low-medium quality of most studies, no data on the TRF, under-representation of some geographical areas, some search-related choices), these data provides Italian practitioners and international researchers of some parameter to evaluate Italian adolescents emotional-behavioral problems. Registered on PROSPERO N. CRD42022299999.

Marta Barba,1 Matteo Frigerio,2 Tomaso Melocchi,1 Desirèe De Vicari,1 Alice Cola2 1Gynecology and Obstetric Department, University of Milano-Bicocca, Monza, Italy; 2Gynecology and Obstetric Department, Fondazione IRCCS San Gerardo Dei Tintori, Ospedale San Gerardo, Monza, ItalyCorrespondence: Marta Barba, University of Milano-Bicocca, ASST Monza, Ospedale San Gerardo, via G.B. Pergolesi, 33, Monza, 20900, Italy, Tel +39 2339434, Email m.barba8792@gmail.comIntroduction and Hypothesis: Lower urinary tract tears after vaginal delivery are a very rare event, estimated to occur in 0.03– 0.05% of women and may be associated with severe stress urinary incontinence, due to great reduction of urethral resistance resulting in a significant intrinsic urethral deficit. Urethral bulking agents represent an alternative, minimally invasive anti-incontinence procedure in the management of stress urinary incontinence. Our aim is to present the management of severe stress urinary incontinence in a patient with concomitant urethral tear caused by obstetric trauma using a minimally invasive treatment option.Methods: A 39-year-old woman referred to our Pelvic Floor Unit for severe stress urinary incontinence. Our evaluation demonstrated an undiagnosed urethral tear involving the ventral portion of the middle and distal urethra, for about 50% of urethral length. Urodynamic evaluation confirmed the presence of severe urodynamic stress incontinence. After proper counseling, she was admitted to mini-invasive surgical treatment with urethral bulking agent injection.Results: The procedure was completed in 10 minutes and she was successfully discharged home on the same day, and no complications occurred. The treatment resulted in total relief of urinary symptoms, which persists at 6-month follow-up.Conclusion: Treatment with urethral bulking agent injection represents a feasible mini-invasive option to manage stress urinary incontinence related to urethral tears.Keywords: urinary incontinence, bulking agents, obstetric tear, pelvic floor ultrasound

Background and Objectives: Serum alpha-fetoprotein (AFP) is a recognized affordable oncological marker in patients with hepatocellular carcinoma (HCC). However, AFP’s prognostic role has been assessed mainly after specific treatments, and no unanimously recognized cut-offs have been identified. The aim of this study is to investigate the prognostic role of different basal AFP cut-offs on survival and HCC course. Materials and Methods: In this single-center, retrospective study, all patients newly diagnosed with HCC between January 2009 and December 2021 were prospectively enrolled. Only patients suitable for curative HCC treatments were included in the analyses. Patients were stratified according to AFP cut-offs of 20, 200, 400, and 1000 ng/mL, which were correlated with survival outcomes and clinical parameters. Results: A total of 266 patients were analyzed, with a median follow-up time of 41.5 months. Median overall survival (OS) of all cohort was 43 months. At the multivariate Cox-regression analysis, AFP value ≥ 1000 ng/mL correlated with impaired OS (1-year OS: 67% vs. 88%, 5-year OS: 1% vs. 43%; p = 0.005); other risk factors were tumor dimension ≥ 5 cm (HR 1.73; p = 0.002), Child–Pugh class B–C (HR 1.72; p = 0.002), BCLC stage A (vs. 0) (HR 2.4; p = 0.011), and malignant portal vein thrombosis (HR 2.57; p = 0.007). AFP ≥ 1000 ng/mL was also associated with a reduced recurrence-free survival (HR 2.0; p = 0.038), while starting from AFP ≥ 20 ng/mL, a correlation with development of HCC metastases over time (HR 3.5; p = 0.002) was seen. AFP values ≥ 20 ng/mL significantly correlated with tumor size and higher histological grading; starting from AFP values ≥ 400 ng/mL, a significant correlation with Child–Pugh class B–C and female gender was also observed. Conclusions: Basal AFP correlates with relevant outcomes in patients with HCC. It could help identify patients at a higher risk of worse prognosis who might benefit from personalized surveillance and treatment programs. Prospective studies are needed to confirm these results.

Echolucency, a measure of plaque instability associated with increased cardiovascular risk, can be assessed in both the carotid plaque and the plaque-free common carotid intima–media (IM) complex as a gray-scale median (plaque-GSM and IM-GSM, respectively). The impact of specific vascular risk factors on these two phenotypes remains uncertain, including the nature and extent of their influence. This study aims to seek the determinants of plaque-GSM and IM-GSM. Plaque-GSM and IM-GSM were measured in subjects from the IMPROVE study cohort (aged 54–79, 46% men) recruited in five European countries. Plaque-GSM was measured in subjects who had at least one IMTmax ≥ 1.5 mm (n = 2138), whereas IM-GSM was measured in all subjects included in the study (n = 3188). Multiple regression with internal cross-validation was used to find independent predictors of plaque-GSM and IM-GSM. Plaque-GSM determinants were plaque-size (IMTmax), and diastolic blood pressure. IM-GSM determinants were the thickness of plaque-free common carotid intima–media complex (PF CC-IMTmean), height, systolic blood pressure, waist/hip ratio, treatment with fibrates, mean corpuscular volume, treatment with alpha-2 inhibitors (sartans), educational level, and creatinine. Latitude, and pack-yearscode were determinants of both plaque-GSM and IM-GSM. The overall models explain 12.0% of plaque-GSM variability and 19.7% of IM-GSM variability. A significant correlation (r = 0.51) was found between plaque-GSM and IM-GSM. Our results indicate that IM-GSM is a weighty risk marker alternative to plaque-GSM, offering the advantage of being readily measurable in all subjects, including those in the early phases of atherosclerosis where plaque occurrence is relatively infrequent.

Introduction: Medical advancements are expected to lead to a substantial increase in the population of women aged 80 and older by 2050. Consequently, a significant number of individuals undergoing corrective prolapse surgery will fall into the elderly-patient category. The research indicates a notable rise in complications associated with prolapse surgery in patients older than 80, irrespective of frailty and other risk factors. Despite these challenges, the vaginal approach has been identified as the safest surgical method for pelvic organ prolapse (POP) repair in the elderly population. For this reason, we aimed to investigate the efficacy, complication rate, and functional outcomes associated with vaginal hysterectomy and an apical suspension/high uterosacral ligaments suspension as a primary technique for prolapse repair, both within a cohort of elderly patients. Methods: We retrospectively analyzed patients who underwent transvaginal hysterectomy plus an apical suspension procedure for stage ≥ II and symptomatic genital prolapse between January 2006 and December 2013. Anatomical and functional outcomes were evaluated. The Patient Global Impression of Improvement (PGI-I) score was used to evaluate subjective satisfaction after surgery. Results: Sixty-five patients were included in the analysis. The median age was 81.3 years. All individuals exhibited an anterior compartment prolapse stage II or higher, and the majority also a central prolapse stage II or higher. Notably, all participants reported symptoms of vaginal bulging. Over half of the population (58.6%) complained of incomplete bladder emptying. The intervention for all participants involved a vaginal hysterectomy with an apical suspension. Sixty-three patients (96.9%) and forty-four patients (67.6%) underwent a simultaneous anterior or posterior repair, respectively. Long-term complications (>30 days from surgery) were observed during follow-up, with a median duration of 23 ± 20 months. Seven (10.7%) anatomical recurrences were recorded, five (7.69%) concerning the anterior compartment, one (1.5%) the central, and three (4.6%) the posterior. Nevertheless, none of them necessitated further surgical intervention due to symptoms. Significant anatomical improvements for the anterior, central, and posterior compartments were noticed, compared to preoperative assessment (p < 0.001 for Aa and Ba, p < 0.001 for Ap and Bp, and p < 0.001 for C). PGI-I values established that 100% of patients were satisfied (PGI-I ≥ 2), with a median score of 1.12. Consequently, objective and subjective cure rates were 89.5% and 100%, respectively. Conclusion: Vaginal hysterectomy combined with apical suspension, particularly high uterosacral ligaments suspension, is a safe and effective primary surgical approach, even in elderly patients.

An emerging research niche has focused on the link between social determinants of health and diabetes mellitus, one of the most prevalent non-communicable diseases in modern society. The aim of the present mini-review is to explore and summarize current findings in this field targeting high-income countries. In the presence of disadvantaged neighborhood factors (including socioeconomic status, food environment, walkability and neighborhood aesthetics), diabetes prevention and care are affected at a multidimensional level. The vast majority of the included studies suggest that, besides individual risk factors, aggregated neighborhood inequalities should be tackled to implement effective evidence-based policies for diabetes mellitus.

Abstract The widely overlapping physicochemical properties of lipoproteins (LPs) and extracellular vesicles (EVs) represents one of the main obstacles for the isolation and characterization of these pervasive biogenic lipid nanoparticles. We herein present the application of an atomic force microscopy (AFM)‐based quantitative morphometry assay to the rapid nanomechanical screening of mixed LPs and EVs samples. The method can determine the diameter and the mechanical stiffness of hundreds of individual nanometric objects within few hours. The obtained diameters are in quantitative accord with those measured via cryo‐electron microscopy (cryo‐EM); the assignment of specific nanomechanical readout to each object enables the simultaneous discrimination of co‐isolated EVs and LPs even if they have overlapping size distributions. EVs and all classes of LPs are shown to be characterised by specific combinations of diameter and stiffness, thus making it possible to estimate their relative abundance in EV/LP mixed samples in terms of stoichiometric ratio, surface area and volume. As a side finding, we show how the mechanical behaviour of specific LP classes is correlated to distinctive structural features revealed by cryo‐EM. The described approach is label‐free, single‐step and relatively quick to perform. Importantly, it can be used to analyse samples which prove very challenging to assess with several established techniques due to ensemble‐averaging, low sensibility to small particles, or both, thus providing a very useful tool for quickly assessing the purity of EV/LP isolates including plasma‐ and serum‐derived preparations.

Background Combining naturalistic enclosure design and animal welfare with visitor interests and education can be challenging for zoos and wildlife parks. To accomplish both purposes, different types of enrichment (food-based or non-food-based items, such as environmental, sensory, cognitive, social) can be used. The aim of the present study is to investigate the effect of food-based and olfactory enrichments on enclosure use, behavior, and visibility of captive brown bears (Ursus arctos), pine martens (Martes martes), domestic ferrets (Mustela putorius furo), and golden jackals (Canis aureus). Methods We used observational approaches to measure enclosure use, behavior, and visibility during three different experimental phases: (1) pre-enrichment (baseline, no experience with the enrichment yet), (2) during enrichment (enrichment was provided at low frequented locations in the enclosures that are easily visible to visitors), and (3) post-enrichment (enrichment was removed from the enclosures). Results We found that enrichment led to a uniform use of the enclosure and enhanced visibility in brown bears, increased activity budgets in pine martens, and observed high object interaction in both species. No effects of enrichment were detected in domestic ferrets. Golden jackals did not leave their burrows during daytime during the entire observation period; thus, observations were not possible at all. Our results suggest different effects of food-based enrichment, e.g., enclosure use, temporal activity patterns, and animal visibility. However, further studies should control for the specific role of the factors involved. Our study represents one of the first explorations of food-based enrichment in rather understudied species.

The extracellular space is nanostructured, populated by heterogeneous classes of nanoparticles, e.g., extracellular vesicles and lipoproteins, which “made by cells for cells'' mediate intercellular, inter-organ, cross-species, and cross-kingdom communication. However, while techniques to study ENP biology in-vitro and in-vivo are becoming available, knowledge of their colloidal and interfacial properties is poor, although much needed. This paper experimentally shows, for the first time, that the aggregation of citrate-capped gold nanoparticles (AuNPs) triggered by lipid vesicle membranes and the related characteristic redshift of the plasmonic signature also applies/extends to lipoproteins. Such interaction leads to the formation of AuNP-lipoprotein hybrid nanostructures and is sensitive to lipoprotein classes and AuNP/lipoprotein molar ratio, paving the way to further synthetic and analytical developments.

BackgroundSlow pathway (SP) ablation is the cornerstone for atrioventricular nodal reentry tachycardia (AVNRT) treatment, and a low-voltage bridge offers a good target during mapping using low x-ray exposure. We aimed to assess a new tool to identify SP by activation mapping using the last CARTO3® version, i.e., CARTO PRIME® V7 (Biosense Webster, Diamond Bar, CA, USA)Methods and resultsRight atrial septum and triangle of Koch 3D-activation map were obtained from intracardiac contact mapping during low x-ray CARTO 3® procedure. In 60 patients (mean age 60.3 ± 14.7, 61% females) undergoing ablation for AVNRT, an automatic activation map using a DECANAV® mapping catheter and CARTO® Confidense™, Coherent, and FAM DX software modules were obtained. The SP was identified in all patients as the latest atrioventricular node activation area; RF catheter ablation (RFCA) in that region elicited junctional beats. The mean procedural time was 150.3 ± 48.3 min, the mean fluoroscopy time exposure was 2.9 ± 2 min, the mean dose-area product (DAP) was 16.5 ± 2.7 cGy/cm2. The mean number of RF applications was 3.9 ± 2, the mean ablation index was 428.6 ± 96.6, and the mean contact force was 8 ± 2.8 g. There were no adverse event during the procedure, and no AVNRT recurrences occurred during a mean follow-up of 14.3 ± 8.3 months.ConclusionAblation of the SP by automatic mapping using Confidense™, Coherent, and FAM DX software modules is an innovative, safe, and effective approach to AVNRT ablation. The CARTO3® V7 system shows on a 3D map the latest AV node activation area during sinus rhythm allowing low fluoroscopy time and highly effective RFCA.

BackgroundThe severity, progression, and outcomes of motor and non-motor symptoms in Parkinson’s disease (PD) are quite variable. Following PD cohorts holds promise for identifying predictors of disease severity and progression.MethodsPD patients (N = 871) were enrolled at five sites. Enrollment occurred within 5 years of initial motor symptom onset. Disease progression was assessed annually for 2-to-10 years after onset. Group-based trajectory modeling was used to identify groups differing in disease progression. Models were developed for UPDRS-III scores, UPDRS-III tremor and bradykinesia-rigidity subscores, Hoehn & Yahr (H&Y) stage, Mini-Mental Status Exam (MMSE) scores, and UPDRS-III, H&Y and MMSE scores considered together. Predictors of trajectory-group membership were modeled simultaneously with the trajectories. Kaplan–Meier survival analysis evaluated survival free of PD outcomes.ResultsThe best fitting models identified three groups. One showed a relatively benign, slowly progressing trajectory (Group 1), a second showed a moderate, intermediately progressing trajectory (Group 2), and a third showed a more severe, rapidly progressing trajectory (Group 3). Stable trajectory-group membership occurred relatively early in the disease course, 5 years after initial motor symptom. Predictors of intermediate and more severe trajectory-group membership varied across the single variable models and the multivariable model jointly considering UPDRS-III, H&Y and MMSE scores. In the multivariable model, membership in Group 2 (28.4% of patients), relative to Group 1 (50.5%), was associated with male sex, younger age-at-onset, fewer education-years, pesticide exposure, absence of reported head injury, and akinetic/rigid subtype at initial presentation. Membership in Group 3 (21.3%), relative to Group 1, was associated with older age-at-onset, fewer education-years, pesticide exposure, and the absence of a tremor-predominant subtype at initial presentation. Persistent freezing, persistent falls, and cognitive impairment occurred earliest and more frequently in Group 3, later and less frequently in Group 2, and latest and least frequently in Group 1. Furthermore, autonomic complications, dysphagia, and psychosis occurred more frequently in Groups 2 and 3 than in Group 1.ConclusionModeling disease course using multiple objective assessments over an extended follow-up duration identified groups that more accurately reflect differences in PD course, prognosis, and outcomes than assessing single parameters over shorter intervals.